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Potassium Phosphate, Tribasic → 5-(3-(6-cyclopropylpyrazin-2-yl)-6-fluoro-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,3,4-oxadiazol-2-amine

HRID 634305
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 634305
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6](B3OC(C)(C)C(C)(C)O3)=[CH:7][N:8]2[S:11]([C:14]2[CH:20]=[CH:19][C:17]([CH3:18])=[CH:16][CH:15]=2)(=[O:13])=[O:12])=[CH:4][C:3]=1[C:30]1[O:34][C:33]([NH:35][CH:36]([CH3:38])[CH3:37])=[N:32][N:31]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.Br[C:74]1[CH:79]=[N:78][CH:77]=[C:76]([CH:80]2[CH2:82][CH2:81]2)[N:75]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:80]1([C:76]2[N:75]=[C:74]([C:6]3[C:5]4[C:9](=[CH:10][C:2]([F:1])=[C:3]([C:30]5[O:34][C:33]([NH:35][CH:36]([CH3:37])[CH3:38])=[N:32][N:31]=5)[CH:4]=4)[N:8]([S:11]([C:14]4[CH:15]=[CH:16][C:17]([CH3:18])=[CH:19][CH:20]=4)(=[O:13])=[O:12])[CH:7]=3)[CH:79]=[N:78][CH:77]=2)[CH2:82][CH2:81]1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

6

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 457883052-Bromo-6-cyclopropylpyrazineHCID 683280445-(6-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,3,4-oxadiazol-2-amine

Produkt 1

HCID 68328349
5-(3-(6-cyclopropylpyrazin-2-yl)-6-fluoro-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,3,4-oxadiazol-2-amine
Ausbeute 36,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysator

Reaktionsbedingungen

Temperatur
130 °C

Versuchsvorschrift

A 20 mL microwave vial was charged with 5-(6-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,3,4-oxadiazol-2-amine (185 mg, 0.342 mmol), Xphos (Strem Chemicals, Newburyport, Mass., 9.8 mg, 0.021 mmol), Pd2(dba)3 (Strem Chemicals, Newburyport, Mass., 9.4 mg, 10.27 μmol), 2-bromo-6-cyclopropylpyrazine (CombiPhos Catalyst Inc., Princeton, N.J., 82 mg, 0.411 mmol) and potassium phosphate (218 mg, 1.03 mmol) followed by purging with argon. The solids were then treated with dioxane (4.0 mL) and water (1.0 mL) and heated in the microwave at 130° C. for 20 min. The reaction mixture was treated with water and extracted with EtOAc, dried over MgSO4, filtered and concentrated. Purification of the crude residue on the ISCO Combiflash Rf (12 g Redisep column, using a gradient of 0-100% EtOAc in hexanes) afforded 5-(3-(6-cyclopropylpyrazin-2-yl)-6-fluoro-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,3,4-oxadiazol-2-amine (65.8 mg, 0.124 mmol, 36.1% yield) as an off-white solid. MS (ESI, pos. ion) m/z: 533.0 (M+H)+. The material was used in the subsequent step without further purification.

Aufarbeitung

  1. customby purging with argon
  2. additionThe solids were then treated with dioxane (4.0 mL) and water (1.0 mL)
  3. additionThe reaction mixture was treated with water
  4. extractionextracted with EtOAc
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification of the crude residue on the ISCO Combiflash Rf (12 g Redisep column

Quellen und Nachweise

ORD-Eintrag
ord-0f13af6cab73471b8ac9b316af53ba10
Quelldatensatz
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09321756B2

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